tbuckley/cabot-search huggingface dataset:
Axillary dissection 10 years after Z0011.
Authors: Magda Palka-Kotlowska, Sara Custodio-Cabello, Luis Cabezon-Gutierrez, Eduardo Oliveros-Acebes, Parham Khosravi-Shahi, Lorenzo Rabadan-Ruiz
Journal: Journal of Clinical Oncology (2022)

e12582 Background: Axillary involvement is one of the strongest prognostic factors in breast cancer. Axillary lymphadenectomy (AL) has been considered one of the milestones to reduce relapse risk of local breast carcinoma. Z0011 trial, demonstrated that axillary dissection was not necessary in cases with one or two nodes involved. The authors proposed 3 sentinel nodes to decide if AL should be done. Since in the trials that explored the omission of lymphadenectomy obtained between one and six nodes, there is no consensus about how many lymph nodes should be obtained in the axillary sampling. The objective of this study is to obtain real data about axillary staging in real practice after Z0011 trial. Methods: 197 patients were selected from clinical records of Hospital Universitario de Torrejon. All patients were diagnosed with localized infiltrating breast carcinoma between 2016 and 2021. All were candidates for sentinel node biopsy (SNB) analyzed by OSNA or histopathology analysis. Patients with in situ tumors, those who underwent neoadjuvant chemotherapy We retrospectively reviewed the number of axillary nodes obtained in SNB and if axillary dissection was performed or not. Results: From 197 patients, 150 were included in the study (47 were excluded because were diagnosed with in situ carcinoma, received neoadjuvant chemotherapy or followup was lost). All 150 women were patients with infiltrating breast cancer who underwent conservative surgery or mastectomy and SNB. After surgical treatment, all patients received subsequent therapies indicated in each case (chemotherapy, radiotherapy or hormone therapy). Medium age at diagnosis was 57 years (range 30-87). Median number of sentinel nodes obtained in SNB was 2 (range 1 to 5). 40 patients had tumor infiltration in SNB, but only 15 underwent axillary dissection,10 of them had one node involved, 4 had 2 nodes involved and one had 3 nodes involved, from up to four extracted. 5 patients had more node involved than those found on the sentinel node biopsy, and all had macrometastasis. Capsular rupture was identified in 7 cases. None of the patients had relapse until the time of follow up was closed. Conclusions: Rate of axillary dissection after Z0011 has decreased without increasing risk of loco-regional or distant relapse. During the time of surgery, not always is possible to obtain 3 sentinel nodes, which could involve more aggressive surgery and comorbidities. Techniques of sentinel node identification are needed and further investigation to resolve in which cases axillary dissection is unavoidable.
Is the BRAF mutation still an unfavorable risk factor in patients with metastatic melanoma in the era of modern therapies?
Authors: Bozena Cybulska-Stopa, Anna Malgorzata Czarnecka, Krzysztof Ostaszewski, Karolina Piejko, Marcin Zietek, Robert Dziura, Ewa Rutkowska, Łukasz Galus, Jacek Calik, Agata Sałek-Zań, Tomasz Zemelka, Agnieszka Kamycka, Wieslaw Bal, Tomasz Kubiatowski, Pawel Rogala, Tomasz Switaj, Grazyna Kaminska-Winciorek, Rafał Suwiński, Jacek Mackiewicz, Piotr Rutkowski
Journal: Journal of Clinical Oncology (2022)

e21544 Background: BRAF-mutated (MUT) melanoma is characterized by specific clinical features including more aggressive biological behavior than BRAF wild-type (WT) melanoma. BRAF mutations are historically known as negative prognostic factor for to shorter overall survival (OS) in patients with stage IV disease with melanoma. Methods: Consecutive patients with unresectable or metastatic melanoma started treatment with BRAF inhibitors (BRAFi), BRAFi and MEK inhibitors (MEKi) or IT (anti-PD-1 antibody) between 1/Jan/2013 and 31/Dec/2020. Clinical factors including age, gender, primary location of melanoma, ECOG performance status, baseline LDH level, and location of metastases, response to treatment were analyzed. Survival analyses were performed using the Kaplan-Meier method, Log-rank and chi-square tests were used for comparison between groups. Data cut-off was 31/Dec/2021. Results: In total 1456 patients were enrolled. BRAF mutation was found in 723 (49.7%) patients and 733 (50.3%) patients were BRAF WT. All BRAF WT patients received first-line IT, while BRAF MUT patient received first-line treatment with BRAFi (n = 134/723, 18%), BRAFi and MEKi (n = 426, 58%) or anty-PD-1 (n = 173, 24%). BRAF MUT patients were significantly younger (median 60 vs 69; p &lt; 0.0001), had worse ECOG (p = 0.0008), elevated LDH (p &lt; 0.0001), had higher number of metastatic sites (p &lt; 0.0001) and brain metastases (p &lt; 0.0001). The estimated median OS (mOS) in BRAF WT group was 17.3 month while in BRAF MUT - 14.8 months (p = 0.33; HR = 0.94, Cl 95% 0.8-1.1). mOS in BRAF MUT group treated with BRAFi was - 10.0, while with BRAFi and MEKi combination - 14.9. BRAF WT and BRAF MUT groups treated with IT did not differ significantly in baseline characteristics. BRAF MUT group treated with IT achieved mOS of 26.2 months, while in BRAF WT 17.3 months. Conclusions: The analysis showed no differences in the median OS between BRAF MUT and BRAF WT patients with unresectable or metastatic melanoma treated with novel therapies (BRAFi-MEKi combination or IT), despite unfavorable prognostic factors in the BRAF MUT group. Moreover mOS was significantly prolonged in the BRAF MUT patients treated with IT.
Longitudinal outcomes following implementation of baseline PSA risk stratification of men in their forties
Authors: Z.D. Michael, S. Kotamarti, R. Arcot, K. Morris, A. Shah, J. Anderson, A. Armstrong, R. Gupta, G.M. Preminger, J.W. Moul, K. Oeffinger, K. Shah, T.J. Polascik
Journal: European Urology (2022)
Breast cancer: Online education’s effect on clinician ability to assess risk of recurrence and understanding the latest data.
Authors: Urvi Patel, Nabil Dorkhom, Tristin Abair, Davecia Ragoonath Cameron, Jacob Cohen
Journal: Journal of Clinical Oncology (2022)

e12509 Background: Hormone receptor positive breast cancer (HR+ BC) is often diagnosed in the early, curable, stage. Emerging treatment options make it important to educate clinicians on how to identify patients eligible for these options and increase their understanding of the clinical data associated with therapies in HR+/HER2- early breast cancer (EBC). The study objective was to assess the impact of 2 educational activities on HR+/HER2- EBC on oncologists’ knowledge, competence, and confidence related to risk of recurrence and clinical data. Methods: Two online continuing medical education activities were launched in 2021 covering a range of topics focused on identification of patients at high risk of recurrence and the latest clinical trial data for CDK4/6 inhibitors (CDK4/6i) in HR+/HER2- EBC. Educational impact was assessed using a repeated pair design, with knowledge/competence and confidence questions pre- and post-education. Confidence was assessed on a Likert-type scale ranging from not confident to very confident. Questions were designed to assess if certain learning objectives (LOs), covering identified educational gaps, were met. Data was collected from 06/14/2021 to 01/31/2022. Statistical significance was assessed using McNemar’s test ( P &lt; .05 level). Results: 5,544 learners participated in these 2 activities, including 727 oncologists. The LOs were grouped in 3 themes that assessed oncologists’ knowledge/competence and confidence related to identifying patients with HR+/HER2- EBC at high risk of recurrence and understanding the clinical trial data investigating CDK4/6i in this setting. Two themes showed a significant improvement. The number of oncologist learners assessed per theme differed from 228 to 260. Conclusions: Participation in text- and video-based activities resulted in a significant improvement of oncologists’ knowledge, competence, and confidence related to CDK4/6i clinical data and treatment eligibility for patients with HR+/HER2- EBC. Baseline knowledge regarding the identification of high risk of recurrence in HR+/HER2-EBC was high (89% correct responses pre-education) in comparison that of clinical trial data and confidence in identification of patients eligible for adjuvant therapy (54% and 21% respectively). This finding could be reflective of clinicians having a high-level knowledge and competence related to risk stratification prior to the developments that occurred secondary to the approval of CDK4/6i in the adjuvant setting. With these new developments additional education around this topic will be required.[Table: see text]
Characterization of MET exon 14 skipping in pancancer.
Authors: Fei Li, Jing Chen, Xiaoyan Zhang, Dongxiao Yang, Liang Xia, Dazhong Wang, Kai Jin, Jianhua Zhu, Yu Fang, Chunyang Wang, Tonghui Ma, Xingxiang Pu
Journal: Journal of Clinical Oncology (2022)

e20530 Background: MET exon 14 skipping ( METex14) is characterized oncogenic that possesses susceptibility to targeted inhibitors. We retrospectively investigated a Chinese Pan-cancer cohort to characterize METex14 alterations and co-mutation. Methods: We screened tumor tissues or body fluids of a pan-cancer patients by DNA-based next-generation sequencing assay (Genetron Health) from 2017 to 2020. And distribution of co-mutation with METex14 was analyzed. Results: 233 samples from 187 patients (190 tissues and 43 circulating tumor DNA) were identified with METex14. Average age of these METex14 patients was 67.84 ± 12.19 years old, indicating they were characterized by advanced age. The cancer distribution involved METex14 was 95.72% of lung cancer (179 cases), 3.21% of brain tumors (4 glioma blastoma, 1 anaplastic astrocytoma and 1 ependymoma), 0.535% of gastrointestinal stromal tumor (1 case) and 0.535% of sarcoma (1 case). Referring to different transcripts (NM_001127500.1/2 or NM_000245.2), a total of 68 distinct sequence variants of METex14 were identified spanning functional regions: 31 forms in splice donor site (SD, 148 cases, including 1 case of D1010H), 5 in splice acceptor site (SA, 5 cases), 13 in poly-pyrimidine tract (PPT, 15 cases), 19 cover PPT and SA (19 cases). In non-lung cancers, 5 of 8 cases were detected of METex14 variation in SD site. Among the driver coexisting cases of lung cancer, METex14 samples mainly coexisted with MET amplification, EGFR driver mutations and functional fusions. Co-mutation cases with MET amplification (13) and SEMA3D-MET fusion (1) may benefit from MET inhibitors, which may be the same as the samples of METex14 alone. 13 of METex14 cases occurred with MDM2 and 9 of CDK4 amplification, respectively. There were 2 of METex14 cases coexisted with EGFR 19del or L858R, which may benefit from combination or sequential therapies of MET inhibitor and EGFR TKIs. In addition, 2 of METex14 cases were detected with functional fusions (1 ALK-EML4, 1 KIFI5B-RET), resulting in potential benefit from combination of corresponding targeted agents. Among non-lung cancer cases, 2 of 8 case had coexistence of METex14 and MET amplification, 6 of 8 patients had coexistence of METex14 and TP53, similar phenomenon was also observed in lung cancer samples. Conclusions: Here we reported diverse METex14 alterations in a Chinese pan-cancer cohort that contribute to oncogenic transformation. METex14 mutations of pan-cancer mainly occurred in SD site. TP53 was its main co-mutant gene among pan-cancers, and MET amplification was also observed.
MODL-16. Generation of immunocompetent syngeneic allograft mouse models for pediatric diffuse midline glioma
Authors: Aimée du Chatinier, Michaël H Meel, Arvid I Das, Dennis S Metselaar, Piotr Waranecki, Marianna Bugiani, Marjolein Breur, Erin F Simonds, Edbert D Lu, William A Weiss, Juan J Garcia Vallejo, Eelco W Hoving, Timothy N Phoenix, Esther Hulleman
Journal: Neuro-Oncology (2022)

Abstract Diffuse midline gliomas (DMG) are highly aggressive pediatric brain tumors with a grim prognosis. A lack of effective treatment options highlights the critical need to investigate new therapeutic strategies. This includes the use of immunotherapy, which has shown promise in other hard-to-treat tumors. To facilitate immunotherapeutic research in this field, and to complement the existing immunodeficient patient-derived DMG models, we developed three distinct immunocompetent mouse models representing different DMG subtypes, i.e., histone 3 wildtype and histone 3 K27M mutant DMG (H3.3K27M or H3.1K27M), that can be used for preclinical testing of new therapies. We first established primary tumor cell cultures from murine DMG tumors that were generated by brainstem-targeted intra-uterine electroporation (IUE). This method enabled the introduction of DMG-associated mutations within the intact developing brainstem, thereby generating DMG tumors in a spatially and temporally defined manner, while maintaining a genetically identical (isogenic) background. We then created allograft DMG mouse models by orthotopically implanting the established primary cell cultures into syngeneic (C57BL/6) mice. Herewith, we provide an allograft tool that is better suitable for large-scale therapeutic studies and more accessible to the scientific community. Importantly, we demonstrated that these allograft models recapitulate the histopathologic phenotype of human DMG, including their diffuse infiltrative growth and expression of DMG-associated antigens. Furthermore, CyTOF mass cytometry analysis indicated that these murine pontine tumors exhibit a tumor immune microenvironment (TIME) similar to human DMG, characterized by considerable myeloid cell infiltration and a paucity of T-lymphocytes and NK cells. As such, we provide a representative model to further delineate the immune landscape in DMG and to preclinically investigate novel (immuno)therapies. Currently, we are using these immunocompetent models to study the interaction between DMG cells and microglia, and we are investigating how we can modify the immune microenvironment to improve checkpoint inhibition in DMG.
Hepatitis E virus genotype 3 microbiological surveillance by the Spanish Reference Laboratory: geographic distribution and phylogenetic analysis of subtypes from 2009 to 2019
Authors: Milagros Muñoz-Chimeno, Silvia Bartúren, Maira Alejandra García-Lugo, Lucia Morago, Álvaro Rodríguez, Juan Carlos Galán, Alfredo Pérez-Rivilla, Mercedes Rodríguez, Rosario Millán, Manuel del Álamo, Roberto Alonso, Laura Molina, Aitziber Aguinaga, Ana Avellón
Journal: Eurosurveillance (2022)

BackgroundHepatitis E virus genotype 3 (HEV-3) is widely distributed throughout Europe, with incidence of infections increasing in many countries. Belgium, Bulgaria, France, Germany, Italy, the Netherlands and the United Kingdom have reported the distribution of HEV-3 subtypes in cohorts of patients with hepatic disease.AimTo describe the distribution of the HEV-3 subtypes in Spain at national and autonomous community (AC) levels between 2009 and 2019. The study was also extended to Andorra.MethodsOf 5,197 samples received by the National Reference Laboratory during the study, 409 were HEV-RNA-positive. Among these, 294 (71.9%) were further typed based on an ORF2 sequence fragment, or, for a subset of 74, based on the full-coding genome sequence.ResultsHEV-3 was detected in 291 samples. The dominant subtype in Spain was HEV-3f (88.3%; 257/291), which occurred in all ACs, with no change in detection level over time. Within this subtype, three subclusters were characterised: HEV-3f-B, HEV-3f-A1 and HEV-3f-A2. The second most common HEV subtype was the recently described HEV-3m (7%; 21/291), with two subclusters identified: HEV-3m-A, which has been known since 2010, and HEV-3m-B, since 2014. The third most encountered subtype was HEV-3c (4.1%; 12/291), with a frequency not increasing over time, unlike observations in some European countries.ConclusionThe importance of the surveillance of HEV-3 subtype and subcluster circulation is yet to be assessed. This surveillance together with the comprehensive epidemiological characterisation of clinical cases, could support the identification of sources of transmission and the establishment of control measures nationally and internationally.
Endoscopy-guided pharyngoesophageal stent fixation after total laryngectomy
Authors: Victoria Salati, Kishore Sandu, François Gorostidi
Journal: Endoscopy (2022)

The incidence of pharyngoesophageal stricture after total laryngectomy is reported in up to 27 % of cases, in whom 92.5 % require endoscopic dilatations to improve oral intake [1]. The management of benign strictures of the pharynx and cervical esophagus is challenging because of the high incidence of recurrence despite repeated dilatations [2]. Stenting after dilatation reduces recurrence and improves oral feeding but with a migration rate of up to 28.6 % [2] [3].
SWK-10. Survivorship: Education, Clinical Guidelines, and Transition to Adult Care
Authors: Molly Hemenway, Kathleen Dorris, Nicholas Foreman, Shelby Winzent, Erin Kissell, Julie Kasson
Journal: Neuro-Oncology (2022)

Abstract As the cure rates of patients with pediatric brain tumors increases, the long term care needs of the survivors increase as well. Survivorship includes several facets of multidisciplinary care including education, clinical care guidelines, and transition to adult medical care. The neuro-oncology program at a large tertiary care hospital has developed a team to address survivorship needs. The Children’s Oncology Group (COG) Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers was utilized as a backbone that was then customized for neuro-oncology patient education including disease type and treatment. The education was compiled into patient handouts as well as electronic medical record (EMR) statements that can easily be added to a clinic note or letter to referring providers. In addition, a diagnosis and treatment summary was placed both in the EMR as well as given to patients at various time points to ensure long term knowledge. Next, follow-up guidelines and roadmaps were developed and customized to tumor type and treatment received (surgery, radiation, chemotherapy). The roadmaps ensure patients are receiving high-quality comprehensive follow-up and screening from a large multidisciplinary team. Finally, patients will transition to adult care. With a large seven state catchment area, the adult care providers vary on local provider availability, knowledge, and medical complexity of the survivor. Each patient is evaluated based on their needs, availability of care locally, and ability to travel. The team developed relationships with the clinical team at the academic center adjacent to the pediatric hospital to support a smooth transition to adult care. The adult neuro-oncology care team can also serve as a consulting service for local adult providers. The survivorship team will continue to address the complex needs of brain tumor survivors and provide education for a smooth transition to adult care.
Intraoperative quality metrics and association with survival following lung cancer resection.
Authors: Brendan Heiden, Daniel B. Eaton, Su-Hsin Chang, Yan Yan, Martin W. Schoen, Bryan F. Meyers, Benjamin D. Kozower, Varun Puri
Journal: Journal of Clinical Oncology (2022)

8502 Background: Surgical resection remains the preferred treatment for functionally fit patients with clinical stage I non-small cell lung cancer (NSCLC). Process-based intra-operative quality metrics (QMs) are important for optimizing long-term outcomes following curative-intent resection. We sought to characterize overall survival using a novel surgical quality score. Methods: We performed a retrospective cohort study using a uniquely compiled dataset of US Veterans with clinical stage I NSCLC receiving definitive surgical treatment. Based on contemporary treatment guidelines, we defined five surgical QMs: timely surgery (within 12 weeks of diagnosis), minimally invasive approach, anatomic resection via lobectomy, adequate nodal sampling (≥10 nodes), and negative margin. Using a multivariable Cox proportional hazards model, we developed a surgical quality score reflecting the relationship between these QMs and overall survival (OS). We also examined the relationship between this score and disease-free survival (DFS). Results: The study included 9,628 Veterans undergoing surgical treatment between 2006 and 2016. QMs were met as follows: timely surgery (n=6,633, 68.9%), minimally invasive approach (n=3,986, 41.4%), lobectomy (n=6,843, 71.1%), adequate nodal sampling (n=3,278, 34.1%), and negative surgical margin (n=9,312, 96.7%). The median (IQR) follow-up was 6.2 (2.5-11.4) years. A normalized score from 0 (no QMs met) to 100 (all QMs met) was constructed, with higher scores reflecting progressively improved risk-adjusted OS (Table). The median (IQR) OS was 86.8 (37.8-149.6) months in the highest score quintile versus 25.3 (7.1-45.8) months in the lowest score quintile. Recurrence was detected in 2,268 (23.6%) patients. Higher surgical quality score was associated with improved DFS (multivariable-adjusted hazard ratio, aHR 0.494, 95% CI 0.245-0.997). Conclusions: Adherence to intra-operative QMs is associated with markedly improved overall and disease-free survival. Efforts to improve adherence to surgical QMs can dramatically improve patient outcomes following curative-intent resection of early-stage lung cancer. [Table: see text]
CRC-403: A phase 1/2 study of bbT369, a dual targeting CAR T-cell drug product with a gene edit, in relapsed and/or refractory B-cell non-Hodgkin lymphoma (NHL).
Authors: Frederick L. Locke, David Bernard Miklos, Michael Timothy Tees, Aojun Li, Anna Truppel-Hartmann, Ian W. Flinn
Journal: Journal of Clinical Oncology (2022)

TPS7580 Background: Although CD19 directed CAR T cell therapies have improved outcomes for non-Hodgkin's lymphoma (NHL) patients, only about 30-40% of 3L+ patients obtain long term remission after this treatment (Neelapu et al. 2017; Schuster et al. 2019). bbT369, a next generation, dual targeted (CD79a/CD20), gene edited (CBLB gene knock out) autologous CAR T cell therapy was devised to overcome hypothesized mechanisms of CD19 CAR T cell treatment failure including loss/downregulation of target antigen, loss of co-stimulation pathways on tumor cells, exhaustion of CAR T cells, and CAR T cell dysfunction due to an immunosuppressive microenvironment (Shah and Fry 2019). bbT369 uses an OR gated design to limit antigen escape and contains split costimulatory domains (CD28 and 41BB) to enhance T cell activation. Methods: CRC-403 (NCT05169489) is a non-randomized, open label, multi-site phase 1/2 study enrolling relapsed and/or refractory B cell non-Hodgkin’s lymphoma (NHL), including diffuse large B cell lymphoma (DLBCL), high-grade B cell lymphoma (HGBCL), primary mediastinal (thymic) large B cell lymphoma (PMBCL), follicular lymphoma (FL) 3b, and DLBCL transformed from FL (tFL). Patients must have relapsed after ASCT or at least 2 prior lines of therapy. Patients with tFL must be relapsed after receipt of ASCT or at least 2 prior therapies after documentation of transformation. Patients with previous exposure to non-investigational CD19 directed CAR T cell therapy who did not experience disease progression within 6 weeks of initial CAR T cell infusion are eligible for enrollment. Approximately 50 patients will be enrolled in the phase 1 portion. The primary endpoints of the phase 1 portion are determination of the MTD, determination of recommended phase 2 dose (RP2D) and safety. Secondary endpoints include overall response rate, complete response rate, time to response and time to next anti-lymphoma treatment. Exploratory endpoints include DOR, PFS, OS, CAR+ T cell expansion and correlations between clinical response and T cell phenotype or antigen expression on tumor cells. The starting dose of bbT369 will be 50x10 6 CAR+ T cells and a BOIN design will be used for dose escalation/de-escalation decisions during the study. Upon establishment of the RP2D, the phase 2 portion will begin enrollment. Clinical trial information: NCT05169489.